DESCRIPTION, OVERALL (provided by applicant): Recent advances in basic research techniques have led to an explosion of information and interest in the role of gastrointestinal peptides in health and disease. The function of these peptides has been shown to extend beyond their classical role as hormones to include actions as paracrine effectors, neurotransmitters, growth factors and cytokines. Peptides are well known to have a myriad of actions in the gastrointestinal tract, but also to have profound influences on the function of most of the body's organ systems. The ubiquitous distribution and myriad actions of gut peptides served as the catalyst that culminated in the formation of the University of Michigan Gastrointestinal Peptide Research Center;a successful multidisciplinary group of investigators that crosses traditional clinical disciplines and scientific boundaries. Advances in cell biology, biochemistry, and molecular biology have provided tools with which the genetic or molecular links between peptides and clinically relevant disorders of digestive function may be identified. The Center, through its Core laboratories and support of innovative Pilot/Feasibility projects, has provided expertise, technical and financial support that enables investigators to broaden the scope of their research. Our extramural and NIDDK digestive diseases related research base has increased nine fold since the Center's inception in 1984. Since the last renewal the Center focused on three thematic areas that reflect the common research interest of numerous investigators affiliated with the Center. These include 1.) the neurobiology regulating satiety, visceral pain and motility;2.) the roles of peptides in inflammatory digestive disorders such as gastritis, colitis, and pancreatitis and 3.) molecular mechanisms regulating cell growth, differentiation and apoptosis. In response to advances in new technologies we have streamlined our core laboratories into 1.) molecular biology;2.) peptide and proteomics;3.) cell biology and imaging studies and 4.) in vivo studies. New initiatives such as DNA microarray which allows investigators to scale up by several orders of magnitude the number of genes that can be examined simultaneously and proteomics which essentially have eliminated the gap between molecular biology and clinical biochemistry will be added to our core facilities. The Peptide Center has galvanized the activities of a large number of researchers who investigate the actions of gut peptides at the University of Michigan, as well as attract new investigators to this field of research. Through the current application, we are seeking to continue and expand the Center with the hope that together the group will approach questions of fundamental importance in the pathophysiology, diagnosis, and treatment of diseases in man.